A Hybrid Methacrylate-Sodium Carboxymethylcellulose Interpolyelectrolyte Complex: Rheometry and in Silico Disposition for Controlled Drug Release

The rheological behavioral changes that occurred during the synthesis of an interpolyelectrolyte complex (IPEC) of methacrylate copolymer and sodium carboxymethylcellulose were assessed. These changes were compared with the rheological behavior of the individual polymers employing basic viscosity, yield stress, stress sweep, frequency sweep, temperature ramp as well as creep and recovery testing. The rheological studies demonstrated that the end-product of the complexation of low viscous methacrylate copolymer and entangled solution of sodium carboxymethylcellulose generated a polymer, which exhibited a solid-like behavior with a three-dimensional network. Additionally, the rheological profile of the sodium carboxymethylcellulose and methacrylate copolymer with respect to the effect of various concentrations of acetic acid on the synthesis of the IPEC was elucidated using molecular mechanics energy relationships (MMER) by exploring the spatial disposition of carboxymethylcellulose and methacrylate copolymer with respect to each other and acetic acid. The computational results corroborated well with the experimental in vitro drug release data. Results have shown that the IPEC may be suitable polymeric material for achieving controlled zero-order drug delivery.     

Some plasma and saliva pharmacokinetics parameters of rifampicin in the presence of pefloxacin

The effect of pefloxacin on the pharmacokinetics parameters of rifampicin in humans was investigated using plasma and saliva concentrations. Five healthy volunteers (4 male and 1 female), ages 20-35 years, each received 600 mg rifampicin alone, and after a 1-week drug washout period, 600 mg rifampicin plus 500 mg pefloxacin was administered with 350 mL of water. Plasma and saliva concentrations of rifampicin were measured at 7 different time intervals and different pharmacokinetics parameters calculated. Pefloxacin coadministered with rifampicin reduced plasma and saliva elimination half-life, peak plasma concentration, area under the concentration time curve, volume of distribution, minimum absorption time, absorption rate constant, and absorption half-life showed a significant increase (P < 0.05). Time to reach peak plasma concentration was not affected with or without pefloxacin. Pefloxacin increases bioavailability of rifampicin and hence extends its detection in the body as demonstrated by rifampicin being estimated at 24 hours when coadministered with pefloxacin, whereas at 24 hours, it was completely absent when administered alone.     

Cytological and biochemical studies during the progression of alloxan-induced diabetes and possible protection of an aqueous leaf extract of Costus afer

Some plants have proven efficacy in the management of diabetes mellitus, of which Costus afer is one. This study was designed to evaluate the cytological and biochemical properties, and comparative ameliorating effects, of an aqueous extract of Costus afer Ker Gawl.（Costaceae） leaf and glibenclamide（GBM）, in liver, kidney, and pancreatic injury induced by alloxan. Thirty male albino rats were divided into six weight-matched groups. Group one served as the negative control（non-induced and non-treated, control）, while groups 2–6 were alloxan-induced diabetic groups. Group 2 served as a positive control（induced and non-treated, IC）, groups 3–5 were treated with different doses of the extract（375, 750, and 1 125 mg/kg body weight） and glibenclamide, respectively. Body weight, absolute and relative organ weights, food and fluid intake, levels of serum glucose and liver enzymes and kidney parameters were calculated and compared. Hepatocytes, renal tubules, and pancreatic cells of diabetic rats, in diabetic non-treated and treated rats were harvested and examined histopathologically. There was dose dependent amelioration on the injuries induced by alloxan on both hepatocytes, renal tubules, and pancreatic cells after treatment with Costus afer. The glucose level was reduced significantly in the Costus afer treated diabetic rats compared with the non-treated diabetic group. Costus afer leaves seem to be effective against diabetic cell injury induced in rat liver, kidney, and pancreas.     

Effect of chloroquine on the urinary excretion of ciprofloxacin

Ciprofloxacin is an inexpensive antibacterial, whereas chloroquine is an inexpensive antimalarial. The coadministration of chloroquine and ciprofloxacin is easily encountered because both drugs are commonly prescribed to patients in the tropics. Five healthy male volunteers aged 19 to 31 years who were not taking any of the prescribed medications and who had no sensitivity to either ciprofloxacin or chloroquine each received 500 mg ciprofloxacin orally with 250 mL of water, and after a 2-week washout period, 500 mg ciprofloxacin plus 600 mg chloroquine was administered orally with 250 mL of water after providing informed consent. A urine sample (7 mL) was collected just before taking the drug at 8:00 AM representing 0 hour and continued afterward at 1, 2, 4, 8, 12, and 24 hours the next day. The samples were stored at -20 degrees C until analyzed. The minimum inhibitory concentrations by diffusion through agar technique were used for the assay of urine ciprofloxacin. The rate of ciprofloxacin excretion and cumulative urine ciprofloxacin were significantly increased. The coadministration of chloroquine increased the cumulative urinary concentration and excretion rate of ciprofloxacin.     

Propylene glycol-associated renal toxicity from lorazepam infusion

OBJECTIVES: Using data from patients who developed elevations in serum creatinine concentrations while receiving continuous-infusion lorazepam, we sought to determine the correlations between the magnitude of serum creatinine concentration rise and each of the following variables: serum propylene glycol level, cumulative lorazepam dose, and duration of lorazepam administration. An additional objective was to identify clinical markers for propylene glycol toxicity. DESIGN: Retrospective chart review. SETTING: Medical-surgical intensive care unit and burn unit at a university hospital. PATIENTS: Eight patients who developed elevations in serum creatinine concentrations while receiving continuous-infusion lorazepam (range 2-28 mg/hr). MEASUREMENTS AND MAIN RESULTS: The mean cumulative dose of lorazepam was 4305 mg (range 1200-10,920 mg), and the mean propylene glycol level determined at the time of peak serum creatinine concentration was 1103 microg/ml (range 186-3450 microg/ml). Serum creatinine concentrations increased in all eight patients during lorazepam infusion and decreased in seven within 3 days after stopping infusion. A weak-to-moderate correlation existed between the magnitude of the rise in serum creatinine concentration and propylene glycol level (r=0.53). A weak-to-moderate correlation also was identified between cumulative lorazepam dose and magnitude of serum creatinine concentration rise (r=0.43), and a strong-to-moderate correlation was found between duration of lorazepam infusion and magnitude of serum creatinine concentration rise (r=0.60). Propylene glycol levels were strongly correlated with both serum osmolality and osmol gap. CONCLUSION: The patients' increased serum creatinine concentrations are likely to have resulted from exposure to propylene glycol as a result of lorazepam infusion. Serum osmolality and osmol gap may be useful markers for propylene glycol toxicity.     

Single-ventricle physiology

The patient with single-ventricle physiology presents a significant challenge to the intensive care team at all stages of management. An integrated approach that applies a working knowledge of cardiac anatomy, cardiopulmonary physiology, and the basic principles of intensive care is essential to guide management for each individual patient. This management requires cooperative and constructive involvement of surgeons, cardiologists, and intensivists, as well as a nursing and respiratory care team experienced in the management of single-ventricle patients. The outcome of each stage of palliation for single-ventricle lesions should continue to improve as new ideas are developed and as older ideas are subjected to rigorous scientific analyses.